Polymer resin formulation having anti-microbial or anti-cogulability and preparation method thereof

ABSTRACT

The present invention relates to an anti-microbial or anti-coagulating polymer resin and a method for preparing the same, and a medical appliance or instrument using the same, and more particularly to a method for preparing an anti-microbial or anti-coagulating medical polymer resin comprising the steps of simply mixing a polymer resin with at least one kind of pharmaceutically active material without using a solvent. The pharmaceutically active material is preferably an anti-microbial or anti-coagulant. According to the present invention, an anti-microbial or anti-coagulating material that is safe to a human body is mixed with a polymer resin by simple addition in an environmentally favorable non-solvent method, thereby maintaining superior anti-microbial effects even after high temperature molding, minimizing a released amount of anti-microbial to increase anti-microbial effect durability, and solving a toxic problem in a body. Therefore, the present invention can be extensively applied for medical appliances/instruments for a human body.

BACKGROUND OF THE INVENTION

(a) Field of the Invention

The present invention relates to a method for preparing ananti-microbial or anti-coagulating polymer resin, particularly to amethod for preparing a functional polymer resin that can preventsecondary bacterial infection, inhibit coagulation of blood wheninserted into a human body, and maintain superior medicinal efficacydurability even after injection and extrusion molding, by combining amaterial that is safe to a human body, has superior compatibility withmaterials for commonly used medical instruments/appliances, and hassuperior anti-microbial or anti-coagulating properties on the surface ofa product, with various materials for medical instruments/appliancessuch as silicon, etc., in a non-solvent form.

(b) Description of the Related Art

Various forms of organic anti-microbial formulations for conventionalanti-microbial and anti-pollutant functions such as quaternary ammoniumsalt, chlorohexidine, carbendazim, thiazole, azole, Sn types, etc. havebeen reported. However, many of the anti-microbial and anti-pollutantproducts using the above materials have problems including unsecuredsafety due to toxicity, and ecosystem destruction due to release ofenvironmental hormones. Additionally, their anti-microbial effects maybe decreased due to thermal decomposition during high temperatureprocessing, and product deterioration due to yellowing may also occur.Particularly, a polymer resin used in the medical field such as for anartificial blood vessel, an artificial heart, an artificial bone,artificial skin, etc. should be secured safety to a human body, and theyshould be protected from various pathogenic bacteria. However,anti-microbial materials of the prior art cannot completely satisfythese requirements.

Conventional technologies for inhibiting bacterial infection of medicalinstruments/appliances have been disclosed in various publications. Asexamples, U.S. Pat. No. 6,342,250 has disclosed a technology for coatinga pharmaceutically active material on a polymer surface; U.S. Pat. No.5,019,283 has disclosed a technology for coating a pharmaceuticallyactive material selected from Ag and an anti-microbial composition on apolymer surface; and U.S. Pat. No. 5,902,283 has disclosed a technologyfor coating a pharmaceutically active material such as rifamycin,penicillin, ciprofloxacine, etc. on the surface of a catheter.

According to the above-mentioned conventional technologies, ananti-microbial material is coated on a surface by an additional processafter preparing a product, and drugs are eluted by DDS (Drug DeliverySystem) to exhibit surface anti-microbial efficacy. However, they havedisadvantages including process workability, durability and effectdurability, toxic problems due to remaining materials that areexcessively eluted in the body, and formation of volatile organiccompounds (V.O.C) due to the use of an organic solvent for coating.

In addition, when medical instruments/appliances are inserted into ahuman body, they react in the following way with blood to cause bloodcoagulation. Firstly, plasma proteins such as fibrinogen, albumingamma-globulin, etc. are absorbed into the medicalinstruments/appliances. After a protein such as fibrinogen, which causesformation of thromboses, is absorbed, adhesion of blood platelets beginsto cause more adhesion and coagulation of blood platelets to formthromboses. Simultaneously, a blood coagulation system is operated asblood coagulation factors are activated, and finally thrombin activatesfibrinogen into fibrin to coagulate fibrin, thereby generating bloodcoagulation.

In order to solve these blood coagulation problems, studies ontechnologies for preventing blood coagulation by medicalinstruments/appliances (e.g., catheters, stents, artificial bone,artificial articulation) are under progress. As examples, as a methodfor preventing formation of thromboses by inhibiting adhesion of bloodplatelets, a method of using albumin is known (M A Packham, G Evans, M FGlynn, and J F Mustard, The effects of plasma proteins on theinteraction of platelet with glass surfaces, J. Lab. Clin, Med., 73:686-97,1969; G H Ryu. D k Han, Y H Kim, and B G Min, Albumin immobilizedpolyurethane and its blood compatibility, Trans. Am. Soc. Artif. Int.Organs, 38: 644-648, 1992). Additionally, as a method for inhibitingformation of thromboses by inactivation of a coagulation factor, amethod of combining heparin anticoagulant with a living body material isdisclosed in EP 0 294 905 1A; and a method of treating heparin andpolyethyleneoxide together is disclosed in EP 0081 853 1A. However,since these methods also use coating of anti-coagulants on an externalsurface, they cannot overcome the above-mentioned disadvantages ofconventional bacterial infection inhibition technologies.

SUMMARY OF THE INVENTION

In order to solve these problems of the prior art, it is an object ofthe present invention to provide a method for preparing ananti-microbial or anti-coagulating polymer resin that can be easilyprepared and has superior durability and compatibility by combining atleast one kind of anti-microbial or anti-coagulating material, of whichsafety to a human body is secured, with a polymer resin in a non-solventform without using a solvent.

It is another object of the present invention to provide a polymer resinprepared by the above method, which has superior compatibility withpolymers and exhibits superior anti-microbial or anti-coagulatingproperties without being thermally decomposed even after moldingprocessing, and thus can be extensively used for a medical polymerresin, natural rubber, petrochemical product, etc.

It is another object of the present invention to provide ananti-microbial or anti-coagulating polymer resin that can maintain areleased amount of pharmaceutically active material at an appropriatelevel to solve the problem of toxicity by elution, and that can beextensively used for medical instruments/appliances which increasedurability of pharmaceutical effects and do not comprise environmentalhormones.

It is another object of the present invention to provide a method forpreparing an anti-microbial or anti-coagulating medical instrumentcomprising the steps of mixing a polymer resin with a pharmaceuticallyactive material under a non-solvent condition, and molding the mixture.

It is another object of the present invention to provide a method forpreparing a household appliance or industrial appliance such as a foodpackaging film, a food container, a water-purifying apparatus, adrinking water tank, a laundry bath, a refrigerator, etc., or a masterbatch (M/B) or compound.

It is another object of the present invention to provide a medicalinstrument/appliance prepared using the above medical polymer resin.

In order to achieve these objects, the present invention provides amethod for preparing an anti-microbial or anti-coagulating polymerresin, which method comprises the steps of mixing a polymer resin withat least one kind of pharmaceutically active material under anon-solvent condition.

The present invention also provides an anti-microbial oranti-coagulating medical polymer resin prepared by the above method,which has a maximum release concentration of pharmaceutically activematerials of 10 ppm/100 hours in an aqueous solution.

The present invention also provides a method for preparing ananti-microbial or anti-coagulating medical instrument/appliance, whichmethod comprises the steps of a) mixing a polymer resin with at leastone kind of pharmaceutically active material under a non-solventcondition; and b) molding and processing the mixture.

Preferably, the method for preparing a medical instrument/appliancecomprises the step of mixing a silicon resin with a pharmaceuticallyactive material and conducting physical molding and processing at 450 to600° C. for 5 seconds under a non-solvent condition to prepare a siliconcatheter.

In addition, the present invention also provides a method for preparinga master batch or compound, which method comprises the steps of mixing aresin selected from a group consisting of linear low densitypolyethylene (LLDPE), polypropylene (PP), polyethylene (PE),acrylonitrile-butadiene-styrene (ABS) copolymer, polycarbonate (PC),polystyrene (PS), and polyvinylchloride (PVC), with at least one kind ofpharmaceutically active material, and molding and processing at 100 to300° C. under a non-solvent condition.

The present invention also provides an anti-microbial oranti-coagulating medical appliance prepared by the above method.

The present invention also provides an anti-microbial oranti-coagulating master batch or compound prepared by the above method.

The anti-microbial or anti-coagulating master batch can be used forpreparing medical appliances, household appliances, industrialappliances, petrochemical appliances, etc.

The present invention also provides a method for preparing a paint,which method comprises the steps of mixing an anti-microbial materialselected from a group consisting of grepafloxacin, sparfloxacin,clinafloxacin, enoxacin, lemefloxacin, norfloxacin, pipemidic acid,ciprofloxacin, temafloxacin, tosufloxacin, ketoconazole, itraconazole,econazole, isoconazole, fluconazole, miconazole, terbinafine, and a saltthereof, with one or more kinds of polymer resin selected from a groupconsisting of alkyd resin, acryl resin, urethane resin, epoxy resin,phenol resin, urea resin, melamine resin, and a modified resin thereof.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be explained in more detail.

The present invention provides a method for preparing a polymer resinthat has superior compatibility with commonly-used polymer resins andmedical materials and has superior anti-microbial or anti-coagulatingproperties, and a polymer resin prepared by the method. The polymerresin having anti-microbial or anti-coagulating properties prepared bythe method of the present invention can be used for medical appliances,household appliances, industrial appliances, petrochemical appliances,etc., and preferably for medical appliances.

Since the polymer resin prepared by the method of the present inventionis of a non-solvent form as opposed to the conventional resins preparedwith solvent, it can maintain pharmaceutical activity even if molded ata high temperature, it has industrial advantages in terms of productioncost reduction and environmental favorableness, etc., and it canmaintain a release concentration of pharmaceutically active materials atan appropriate level.

In addition, the method of the present invention can solve problems of adecrease in durability due to separation and adhesion of a surfacecoating film due to free flexibility of main material resins, andtoxicity due to excessive drug amounts remaining in a body due to a drugdelivery system at the surface thereof. Additionally, the method of thepresent invention can overcome problems of thermal decomposition ofanti-microbial or anti-coagulating materials during high temperatureprocessing, and thus the polymer resin of the present invention can beused for essential materials and products of the medical field becauseit can prevent yellowing of medical instruments/appliances and inhibitbacterial infection and blood coagulation when inserted into a humanbody.

The polymer resin prepared according to the present invention has amaximum release speed of anti-microbial materials of 10 ppm/100 hrs, andpreferably a maximum speed of 5 ppm/100 hrs.

The anti-microbial or anti-coagulating polymer resin of the presentinvention comprises commonly used polymer resin and at least one kind ofpharmaceutically active material.

The pharmaceutically active material is preferably selected from a groupconsisting of anti-microbials, anti-coagulants and a mixture thereof.

As the anti-microbial, materials known to be safe to a human body can beused. The anti-microbial, which has sterilizing effects or microorganismgrowth-inhibiting effects against bacteria or mold, includes ananti-microbial agent and an anti-fungi and anti-pollutant agent, andanti-microbial, anti-fungi, and anti-pollution effects can be expectedby the combined use thereof.

The anti-microbial agent is preferably selected from a group consistingof grepafloxacin, sparfloxacin, clinafloxacin, enoxacin, lemefloxacin,norfloxacin, pipemidic acid, ciprofloxacine, temafloxacine,tosufloxacine, a salt thereof, and a mixture thereof.

The anti-microbial agent is preferably contained in the anti-microbialpolymer resin of the present invention in an amount of 0.1 to 30 wt %,more preferably in an amount of 1 to 10 wt %. If the content of theanti-microbial agent is less than 0.1 wt %, the anti-microbial effect isslight, and if it exceeds 30 wt %, the improvement effect is notsignificant thus making it uneconomical.

The anti-fungi or anti-pollutant agent is preferably selected from agroup consisting of ketoconazole, fluconazole, itraconazole, econazole,miconazole, isoconazole, terbinafin, a salt thereof, and a mixturethereof.

The anti-fungi or anti-pollutant agent is preferably contained in thepolymer resin of the present invention in an amount of 0.1 to 30 wt %.If the content is less than 0.1 wt %, the anti-fungi effect is slight,and if it exceeds 30 wt %, the improvement effect is not significantthus making it uneconomical.

The anti-coagulant, which prevents coagulation of blood, is selectedfrom a group consisting of warfarin, aspirin, ticlopidine, triflusal,clopidogrel, cilostazol, a salt thereof, and a mixture thereof.

The anti-coagulant is preferably contained in the anti-coagulatingpolymer resin in an amount of 0.1 to 20 wt %, and more preferably 1 to10 wt %. If the content is less than 0.1 wt %, the pharmaceutical effectis slight, and if it exceeds 20 wt %, the improvement effect is notsignificant thus making it uneconomical.

The polymer resin is preferably used for a medical instrument or medicalappliance, and any material that is safe and does not cause side effectscan be used.

As the commonly used polymer resin, silicon resin, ABS, SAN, or LLDPE ispreferably used. In addition, one or more kinds selected from a groupconsisting of polyetherimide (PEI), polyethylene (PE), polypropylene(PP), polycarbonate (PC), polyvinylchloride (PVC), polystyrene (PS),epoxy resin, polytetrafluoroethylene(PTFE), polyacetal (POM), polyamide(PA), polyurethane (PU), ethylene-vinylacetate copolymer (EVA),polymethylmethacrylate (PMMA), polyvinylalcohol (PVA), low densitypolyethylene (LDPE), high density polyethylene (HDPE),polyacrylonitrile, polybutadiene, polyacrylic acid, polyacrylimide,polysulfone, polyamide-imide, polyneoprene, polydimethylsiloxane,polyetheretherketone, polyphenylenesulfide, polyvinylfluoride,polyvinylacetate, polyvinylidinefluoride, polyethersulfone,polycaprolactone (PCL), and a copolymer thereof; natural rubber; and asynthetic rubber can also be used.

Among these, a medical polymer resin is preferably selected from a groupconsisting of polyethylene (PE), polypropylene (PP), polycarbonate (PC),polyvinylchloride (PVC), polystyrene (PS), epoxy resin,polytetrafluoroethylene (PTFE), polyacetal (POM), polyamide (PA),polyurethane (PU), ethylene-vinylacetate copolymer (EVA),polymethylmethacrylate (PMMA), polyvinylalcohol (PVA), polycaprolactone(PCL), and a copolymer thereof; silicon resin; natural rubber; and asynthetic rubber.

In addition, the method for preparing a polymer resin of the presentinvention may further comprise the step of adding one or more kinds ofadditives selected from a group consisting of an antioxidant, aheat-stabilizer, a dispersant, and a lubricant, which are commonly usedin plastic molding processing. Preferably, a dispersant and anantioxidant are also added.

The dispersant functions for uniformly dispersing commonly used resinand pharmaceutically active material. The examples includeN,N′-ethylene-bis-stearamide (E.B.S.), low density polyethylene wax,etc., and they can be used alone or in combination. If used, the E.B.S.functions as a lubricant. The content of the dispersant is preferably0.1 to 15 wt % of the total composition. If the content is less than 0.1wt %, dispersion is slight, and if it exceeds 15 wt %, a further effectimprovement cannot be expected.

The antioxidant is used for preventing and inhibiting productdeterioration such as discoloration due to oxygen in the air. Examplesthereof include 2,6-di-tert-butyl-p-cresol,n-octadecyl-3-(4-hydroxy-3m5-ditert-butylphenyl)propionate,tetrabis[methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate]methane,1,3,5-trimethyl-2,4,6-tris-(3, 5-di-t-butyl-4-hydroxybenzene)benzene,etc. The content of the antioxidant is preferably 0.1 to 2.5 wt % of thetotal composition. If the content is less than 0.1 wt %, theanti-oxidation effect is slight, and if it exceeds 2.5 wt %, a furthereffect improvement cannot be expected.

The heat-stabilizer is used for aiding maintenance of physical andchemical properties of the resin during usage of the final product, andprevention of thermal degeneration during processing. As theheat-stabilizer, zinc stearate [Zn(C17H35COO)2], magnesium stearate[Mg(C17H35COO)2], barium stearate [Ba(C17H35COO)2], etc. can be used.The content of the heat stabilizer is preferably 0.1 to 3.5 wt % of thetotal composition. If the content is less than 0.1 wt %, the heatstabilizing effect is slight, and if it exceeds 3.5 wt %, a furthereffect improvement cannot be expected.

In addition, according to the present invention, a medicalinstrument/appliance can be prepared using the medical polymer resin.The medical instrument/appliance is preferably a medical catheter, aprosthetic hand, a prosthetic foot, an artificial bone, an artificialarticulation, artificial skin, an artificial kidney, a syringe, a bloodtransfusion pack, or an artificial tooth, and more preferably a siliconcatheter, a prosthetic hand or a prosthetic foot. In addition, accordingto the present invention, a master batch or compound can be preparedusing the medical polymer resin. The master batch or compound can beused as a high functional additive in processing of industrialappliances such as food packaging material, plastic, etc., and the addedamount is preferably 0.1 to 30 wt %.

The silicon catheter can be prepared by mixing a silicon resin andpharmaceutically active material, and molding and processing the mixtureunder a non-solvent condition. Additionally, even if molding isconducted at a high temperature of 450 to 600° C./5 sec, pharmaceuticalactivity can be maintained.

In addition, in case an acrylonitrile-butadiene-styrene (ABS) orstyrene-acrylonitrile (SAN) resin is used, a medical polymer resin thatmaintains pharmaceutical activity and has a low release concentration ofpharmaceutically active material can be prepared by mixing the ABS orSAN resin with a pharmaceutically active material and then molding themixture at 210 to 260° C.

In addition, in case a linear low density polyethylene resin (LLDPE) isused, a medical master batch or compound that has identical or superiorpharmaceutical activity to the existing one and has a remarkably lowrelease speed of a pharmaceutically active material can be prepared bymixing the LLDPE with a pharmaceutically active material and molding themixture at 170 to 210° C.

In addition, according to the present invention, the petrochemical orhousehold appliance selected from a group consisting of awater-purifying apparatus, a food packing film, a food container, arefrigerator, a washing machine, a computer and peripheral device, adrinking water tank, a water tub, a bidet nozzle and a toilet cover, adesk and chair, an automobile handle, infant goods, a bathtub, and acosmetic container can be prepared using the master batch or compoundprepared by the above method.

Since the method for preparing a medical appliance of the presentinvention conducts molding under a non-solvent condition, ananti-microbial or anti-coagulating medical instrument or medicalappliance, or a master batch or compound can be provided by a verysimple method. The anti-microbial or anti-coagulating medical instrumentor appliance includes, for example, a silicon catheter, a prostheticfoot, a prosthetic hand, a surgery glove, artificial skin, an artificialkidney, an artificial articulation, an artificial bone, a blood bag, atube, a syringe, and an artificial tooth, but it is not limited thereto.

The anti-microbial or anti-coagulating medical appliance prepared by themethod of the present invention has a maximum release speed ofpharmaceutically active material, for example an anti-microbial, of 10ppm/100 hrs in an aqueous solution, and more preferably a maximum speedof 5 ppm/100 hrs.

In addition, according to the present invention, paint can be preparedby mixing a polymer resin and at least one kind of the anti-microbialand additive. The polymer resin is selected from a group consisting ofalkyd resin, acryl resin, urethane resin, epoxy resin, phenol resin,urea resin, melamine resin, and a modified resin thereof; and theadditive is selected from hydroxypropylacrylate,1,6-hexanedioldiacrylate, pentaerythritoltriacrylate, orpolyethylenedipentaerythritol. If required, commonly used additives suchas a pigment, a diluent, a physical property controlling monomer andoligomer, a polyol (e.g., acryl polyol, urethane polyol, epoxy polyol,urea-melamine polyol, etc.), etc. can be further added to the liquidresin composition. As the physical property controlling monomer, one ormore kinds selected from a group consisting of hydroxypropylacrylate(HPA), 1,6-hexandioldiacrylate (HDDA), pentaerythritol triacrylate(PETA), polyethylenglycoldiacrylate (PEGDA), trimethylolpropaneethoxylate triacrylate (TMPEOTA), and dipentaerythritol hexaacrylate(DPHA) can be used.

The anti-microbial and commonly used resin composition can be used as acoating agent, and natural curing, heat-curing, UV curing treatment,etc. can be involved.

The present invention will be explained with reference to the followingExamples, but they are to illustrate the present invention and thepresent invention is not limited to them.

EXAMPLES Example 1 Preparation of Anti-Microbial Polymer Resins andAnti-Microbial Tests

As an anti-microbial agent, norfloxacin and ciprofloxacin chlorate(hereinafter referred to as ‘ciprofloxacin’), pipemidic acid, andenoxacin were added to and mixed with a commonly used resin with thecomposition as shown in the following Table 1, and zinc stearate as aheat stabilizer and paraffin wax and E.B.S. as a dispersant were addedand all compounds were mixed in a high speed mixer. The composition wasmanufactured into a sample of a size of 4.5×7.0 cm while changing thetemperature from 100 to 300° C. using a preexisting injection moldingapparatus. The bacterial decrease rate was measured according to a shakeflask method using E.coli (KCTC 1682) as a host, of which results are asshown in the following Table 1. TABLE 1 PP LLDPE LDPE HDPE ABS SANCipro-floxacin 5 (wt %) 95 95 95 95 95 95 Bacteria decrease 100 100 100100 99.99 99.99 rate (%) 1 (wt %) 99 99 99 99 99 99 Bacteria decrease99.99 99.99 99.99 99.99 99.99 99.99 rate (%) Nor-floxacin 5 (wt %) 95 9595 95 95 95 Bacteria decrease 100 100 100 100 99.99 99.99 rate (%) 1(wt%) 99 99 99 99 99 99 Bacteria decrease 99.99 99.99 99.99 99.99 99.9999.99 rate (%) Pipemidic acid 5(wt %) 95 95 95 95 95 95 Bacteriadecrease 99.99 99.99 99.99 99.99 99.97 99.97 rate (%) 1 (wt %) 99 99 9999 99 99 Bacteria decrease 99.95 99.97 99.96 99.89 99.95 99.93 rate (%)Enoxacin 5 (wt %) 95 95 95 95 95 95 Bacteria decrease 100 100 100 10099.99 99.99 rate (%) 1 (wt %) 99 99 99 99 99 99 Bacteria decrease 99.9999.99 99.99 99.99 99.96 99.94 rate (%)Each commonly used resin (PP, LLDPE, LDPE, HDPE, ABS, SAN) comprised 0.2wt % of zinc stearate, 0.2 wt % of paraffin wax and 0.25 wt % of E.B.S.

Example 2 Preparation of Anti-Microbial Master Batches andAnti-Microbial Tests

A known anti-microbial, a commercialized commonly used LLDPE resin, adispersant, and an antioxidant were introduced into a high speed mixer,they were stirred at a high speed for about 30 minutes to mix, and thenextrusion molded in an extrusion molding apparatus at a moldingtemperature of 170 to 210° C. to prepare an anti-microbial master batchin a pellet form. Each anti-microbial master batch or compound wasprepared using HDPE and PP by the same method. Each compositional ratiois as shown in Table 2. Anti-microbial tests were conducted by the shakeflask method, of which results are described in Table 3. TABLE 2Composition of anti-microbial master batches Pharmaceutically activematerial Dispersant/ Total (wt %) LLDPE¹⁾ HDPE²⁾ PP³⁾ lubricant⁴⁾Antioxidant⁵⁾ Dispersant⁶⁾ (wt %) Composition 1 Ciprofloxacin 5 82.9 — —2 0.1 10 100 Composition 2 Norfloxacin 5 — 82.9 — 2 0.1 10 100Composition 3 Enoxacin 5 — — 83.4 1.5 0.1 10 100 Composition 4 Pipemidicacid 5 82.9 — — 2 0.1 10 100 Composition 5 Clinafloxacin 5 — 82.9 — 20.1 10 100 Composition 6 Grepafloxacin 5 — — 82.9 2 0.1 10 100Composition 7 Lemefloxacin 5 82.9 — — 2 0.1 10 100 Composition 8Sparfloxacin 5 — 82.9 — 2 0.1 10 100 Composition 9 Temafloxacin 5 — —82.9 2 0.1 10 100 Composition 10 Tosufloxacin 5 82.9 — — 2 0.1 10 100Composition 11 Ciprofloxacin 5 + 77.9 — — 2 0.1 10 100 norfloxacin 5note)¹⁾SK Co. Ltd. Product name CA 110²⁾SK Co. Ltd. Product name JH 910³⁾product name H360F⁴⁾N,N′-ethylene bis stearamide (E.B.S)⁵⁾n-octadecyl-3(3′-5′-di-t-butyl-4-hydroxyphenyl)propionate⁶⁾polyethylene wax

TABLE 3 Anti-microbial test for anti-microbial master batches (unit: %)S. typhi- P. aeru- E. coli S. aureus murium ginosa (KCTC (KCTC (KCTC(KCTC 1682) 1621) 1925) 2004) Composition 1 99.99 99.99 99.99 99.99Composition 2 99.99 99.99 99.99 99.99 Composition 3 99.99 99.99 99.9999.99 Composition 4 99.99 99.99 99.99 99.99 Composition 5 99.99 99.9999.99 99.99 Composition 6 99.99 99.99 99.99 99.99 Composition 7 99.9999.99 99.99 99.99 Composition 8 99.99 99.99 99.99 99.99 Composition 999.99 99.99 99.99 99.99 Composition 10 99.99 99.99 99.99 99.99Composition 11 99.99 99.99 99.99 99.99

Example 3 Preparation of Anti-Microbial Master Batches

Anti-microbial master batches with the compositions as shown in Table 4were prepared by finely powdering one or two components ofciprofloxacin, pipemidic acid, terbinafin chloric acid (hereinafterreferred to as ‘terbinafin’) and miconazole, by the same method as inExample 2, and anti-microbial tests were conducted. The results are asdescribed in Table 5. As a dispersant, N,N′-ethylene bis stearamide(E.B.S.) and polyethylene wax were used, and as an antioxidant,n-octadecyl-3(3′5′-di-t-butyl-4-hydroxyphenyl)propionate) was used.TABLE 4 Compositions of anti-microbial master batches Cipro- PipemidicMicon- Dispersant/ Anti- Total LLDPE floxacin acid Terbinafin azolelubricant oxidant Dispersant (wt %) Composition 12 84.9 1 — 2 — 2 0.1 10100 Composition 13 84.9 1 — — 2 2 0.1 10 100 Composition 14 82.2 — 1 2 —1.5 0.3 13 100 Composition 15 82.2 — 1 — 2 1.5 0.3 13 100

TABLE 5 Anti-microbial test for anti-microbial master batch StrainComposition 12 Composition 13 Composition 14 Composition 15Anti-microbial¹⁾ E. coli (KCTC 1682) 8 mm ± 1 mm 9 mm ± 1 mm 8 mm ± 1 mm10 mm ± 1 mm

S. typhimurium (KCTC 1925) 11 mm ± 1 mm  11 mm ± 1 mm  10 mm ± 1 mm  10mm ± 1 mm S. aureus (KCTC 1621) 9 mm ± 1 mm 8 mm ± 1 mm 8 mm ± 1 mm  7mm ± 1 mm Anti-fungi²⁾ C. albicans (KCTC 7729) 0 grade 0 grade 0 grade 0grade A. flavus (KCTC 6961) 0 grade 0 grade 0 grade 0 gradeAnti-pollutant³⁾ Pass pass pass PassNote)¹⁾measured by ASTM G22²⁾measured by ASTM G21Grade: 0 grade - Mold did not grow on a sample.1 grade - Mold grew within 10% on a sample.2 grade - Mold grew 10 to 30% on a sample.3 grade - Mold grew 30 to 60% on a sample.4 grade - Mold grew 60% or more on a sample.

Example 4 Preparation of Anti-Microbial Films using Anti-MicrobialMaster Batch

Anti-microbial packaging films were prepared by adding theanti-microbial master batch of Composition 1 of Example 2 respectivelyto LDPE and CPP in an amount of 5%. Anti-microbial tests were conductedby ASTM G22. As a control, common LDPE and CPP films to which theanti-microbial master batch was not added were used. The results are asdescribed in Table 6. TABLE 6 Anti-microbial test for anti-microbialfilm E. coli S. typhimurium K. pneumoniae (KCTC 1682) (KCTC 1925) (KCTC1621) Control LDPE 0 mm 0 mm 0 mm Example 4-1 6 mm ± 1 mm 11 mm ± 1 mm 9 mm ± 1 mm Control CPP 0 mm 0 mm 0 mm Example 4-2 8 mm ± 1 mm 13 mm ±1 mm 10 mm ± 1 mm

Example 5 Preparation of Anti-Microbial Cutting Boards

Anti-microbial cutting boards with a size of 24 cm×40 cm were preparedby respectively adding 1 wt %, 3 wt %, and 5 wt % of the anti-microbialmaster batches of Composition 1 of Example 2 to high densitypolyethylene (HDPE) resin. Injection molding was conducted at 170 to210° C. In order to confirm durability of anti-microbial effects, afterleaving the boards in flowing tap water for 30 days, anti-microbialeffects before and after were compared. Results are as described inTable 7 (ASTM G22). TABLE 7 Anti-microbial test for anti-microbialcutting boards 1 wt % add 3 wt % add 5 wt % add initial After 30 daysinitial After 30 days initial After 30 days E. coli 2.5 mm ± 1 mm 2.0 mm± 1 mm 5.5 mm ± 1 mm 5.0 mm ± 1 mm 5.2 mm ± 1 mm 5.1 mm ± 1 mm (KCTC1682) S. typhimurium 3.5 mm ± 1 mm 3.0 mm ± 1 mm 7.0 mm ± 1 mm 6.5 mm ±1 mm 7.5 mm ± 1 mm 7.2 mm ± 1 mm (KCTC 1925)

Example 6 Preparation of Anti-Microbial Foly Catheters andAnti-Microbial Test

Anti-microbial foly catheters in the form of tubes were prepared by rollmixing a silicon resin, ciprofloxacin, and a catalyst with thecomposition of Table 8 for 30 to 60 minutes in an extrusion moldingapparatus. Molding was conducted at 450 to 600° C./5 sec. The moldedproducts were cured for 2 hours while maintaining them at 200° C. in adrier to remove remaining solvent. Anti-microbial test results are asdescribed in Table 9. Anti-microbial effects were measured by ASTM G22(measuring inhibited circle). TABLE 8 Compositions of anti-microbialfoly catheters Peroxide Pt cipro- Silicon Total catalyst catalystfloxacin resin (wt %) Composition 16 — 0.2 0.3 99.5 100 Composition 170.2 — 0.1 99.7 100 Composition 18 0.2 — 0.3 99.5 100 Composition 19 0.2% — 1.0 98.8 100 Composition 20 0.2 — 3.0 96.8 100 Composition 210.2 — 5.0 94.8 100

TABLE 9 Anti-microbial test for anti-microbial foly catheters S. aureusE. coli P. aeruginosa (AATC 1621) (AATC 1682) (AATC 2004) Composition 162.0 ± 0.1 mm 0.5 ± 0.1 mm 1.0 ± 0.1 mm Composition 17 2.0 ± 0.1 mm 0.5 ±0.1 mm 1.0 ± 0.1 mm Composition 18 2.0 ± 0.1 mm 2.0 ± 0.1 mm 1.5 ± 0.1mm Composition 19 6.0 ± 0.1 mm 7.5 ± 0.1 mm 6.5 ± 0.1 mm Composition 2014.0 ± 0.1 mm  10.0 ± 0.1 mm  7.5 ± 0.1 mm Composition 21 14.0 ± 0.1 mm 10.5 ± 0.1 mm  7.5 ± 0.1 mm

Example 7 Preparation of Anti-Microbial Silicon Prosthetic Feet andAnti-Microbial Test

Anti-microbial prosthetic feet were prepared by roll mixing siliconresin and ciprofloxacin with the compositions of Table 10 respectivelyfor 2 hours, introducing it into a mold to reflux for 1 hour whilemaintaining it at 160° C., and then cooling to room temperature.Anti-microbial performance was examined by measuring the bacteriadecrease rate using the shake flask method. Results are as described inTable 11.

1) Shake flask method conditions:

Test bacterial fluid was shaken at 25° C. 150 times/min.

2) Bacteria decrease rate was measured by the following Equation 1.

[Equation 1]Decrease rate=(number of bacteria in blank after 24 hours−number ofbacteria in sample after 24 hours)/ (number of bacteria in blank after24 hours−number of bacteria)×100

TABLE 10 Compositions of anti-microbial prosthetic feet ciprofloxacinSilicon resin Total (wt %) Composition 22 1.0 99.0 100 Composition 233.0 97.0 100 Composition 24 5.0 95.0 100 Composition 25 10 90.0 100

TABLE 11 Anti-microbial test for anti-microbial silicon prosthetic feet.Number of bacteria Immediately Decrease after After rate inoculation 24hours (%) S. aureus Blank 5.0 × 10⁵   683 × 10⁹ — (ATCC 6538)composition 22 5.0 × 10⁵ 0 100 composition 23 5.0 × 10⁵ 0 100composition 24 5.0 × 10⁵ 0 100 composition 25 5.0 × 10⁵ 0 100 P.aeruginosa Blank 5.0 × 10⁵   1.72 × 10¹⁰ — (ATCC 27853) composition 225.0 × 10⁵   6.0 × 10² 99.99 composition 23 5.0 × 10⁵ 0 100 composition24 5.0 × 10⁵ 0 100 composition 25 5.0 × 10⁵ 0 100

EXAMPLE 8 Preparation of Anti-Microbial or Anti-Coagulating MasterBatches and Anti-Microbial or Anti-Coagulating Test

Medical master batches with the compositions of Table 12 were preparedby adding 2 components of warfarin, ticlopidine, and clopidogrel, whichare known anti-microbial and anti-coagulating materials, to polyurethane(PU) resin, polypropylene (PP) resin, or linear low density polyethylene(LLDPE), which are commonly used medical polymer resins, in anon-solvent process. Anti-microbial effects were examined by the shakeflask method, and the results are as described in Table 13. TABLE 12Compositions of anti-microbial and anti-coagulating master batchesPharmaceutically total active material (wt %) PU PP LLDPE (wt %)Composition 26 Warfarin 5 95 — — 100 Composition 27 Warfarin 5 — 95 —100 Composition 28 Warfarin 5 — — 95 100 Composition 29 Ciprofloxacin5 + 90 — — 100 warfarin 5 Composition 30 Ciprofloxacin 5 + — 90 — 100clopidogrel 5 Composition 31 Ciprofloxacin 5 + — — 90 100 ticlopidine 5Composition 32 Norfloxacin 5 + 90 — — 100 clopidogrel 5 Composition 33Norfloxacin 5 + — 90 — 100 warfarin 5 Composition 34 Norfloxacin 5 + — —90 100 ticlopidine 5Note)Each resin (PU, PP, LLDPE) comprised 0.2 wt % of zinc stearate, 0.2 wt %of paraffin wax, and 25 wt % of E.B.S.

TABLE 13 Anti-microbial test for anti-microbial or anti-coagulatingmaster batches E. coli S. aureus S. typhimurium B. subtilis K.pneumoniae (KCTC 1682) (KCTC 1621) (KCTC 1925) (KCTC 1021) (KCTC 2690)Composition 26 0 0 0 0 0 Composition 27 0 0 0 0 0 Composition 28 0 0 0 00 Composition 29 99.99 99.99 99.99 99.99 99.99 Composition 30 99.9999.99 99.99 99.99 99.99 Composition 31 99.99 99.99 99.99 99.99 99.99Composition 32 99.99 99.99 99.99 99.99 99.99 Composition 33 99.99 99.9999.99 99.99 99.99 Composition 34 99.99 99.99 99.99 99.99 99.99

Anti-Coagulation Test for Anti-Microbial or Anti-Coagulating MasterBatches

A Sprague-Dawley rat (Korean Biolink) with a body weight of 250 to 300 gwas etherized, and then 3.6 ml of blood was taken with a 25 ml syringeby a heart perforation method. In order to inhibit blood coagulation,0.4 ml of 3.8% sodium citrate was previously introduced into thesyringe, and the blood taken was instantly used for the test.

The master batches (M/B) of Compositions 26 to 34 and a control masterbatch that did not contain pharmaceutically active material wererespectively immersed in the rat blood solution, and then after 1 hour,anti-coagulation effects were compared. Results are as described inTable 14. TABLE 14 After 20 After 40 After 60 minutes minutes minutesControl PU + ++ +++ Control PP + ++ +++ Control LLDPE + ++ +++Composition 26 − + + Composition 27 − + + Composition 28 − + +Composition 29 − + + Composition 30 − + + Composition 31 − + +Composition 32 − + + Composition 33 − + + Composition 34 − + +Note)+++: Surface blood coagulation seriously appeared.++: Surface blood coagulation appeared.+: Surface blood coagulation slightly appeared.−: No surface blood coagulation appeared

Control PU, PP, and PE master batches showed serious blood aggregationafter 1 hour, while master batches comprising the anti-coagulant showeddelayed blood coagulation. As can be seen from the results of Tables 13and 14, anti-microbial and anti-coagulation effects were maintained evenafter molding processing.

Example 9 Preparation of Anti-Microbial or Anti-Coagulating Polyurethane(PU) Catheters and Anti-Microbial or Anti-Coagulation Test

Anti-microbial or anti-coagulating polyurethane catheters were preparedby roll mixing anti-microbial ciprofloxacin and norfloxacin andanti-coagulant norfloxacin with medical polyurethane (PU) with thecompositions of Table 15, introducing it into a mold to reflux for 1hour while maintaining it at 160° C., and then cooling to roomtemperature. Anti-microbial performance was examined by the shake flaskmethod, and the results are described in Table 16. Anti-coagulationperformance results are as described in Table 17. TABLE 15 Compositionsof anti-microbial or anti-coagulating polyurethane Poly- Anti- urethaneTotal coagulant Anti-microbial resin (wt %) Composition 35 —ciprofloxacin 3.0 97.0 100 Composition 36 — norfloxacin 3.0 97.0 100Composition 37 Warfarin 3 — 97.0 100 Composition 38 Warfarin 3 — 97.0100 Composition 39 Warfarin 3 ciprofloxacin 3.0 94.0 100 Composition 40Warfarin 3 norfloxacin 3.0 94.0 100

TABLE 16 Anti-microbial test for anti-microbial or anti-coagulatingpolyurethane catheter S. aureus E. coli P. aeruginosa (AATC 1621) (AATC1682) (AATC 2004) Composition 35 99.99 99.99 99.99 Composition 36 99.9999.99 99.99 Composition 37 0 0 0 Composition 38 0 0 0 Composition 3999.99 99.99 99.99 Composition 40 99.99 99.99 99.99

Anti-coagulating tests for anti-microbial or anti-coagulatingpolyurethane catheters were conducted by the same method as in Example8. The polyurethane catheter samples of Compositions 35 to 40 and thepolyurethane catheter that did not comprise a pharmaceutically activematerial were immersed in the rat blood solution, and after 1 hour,anti-coagulating effects were compared. The results are as described inTable 17 TABLE 17 Anti-coagulating test for anti-microbial oranti-coagulating polyurethane catheter After 20 min. After 40 min. After60 min. Control PU + ++ +++ Composition 35 + ++ +++ Composition 36 + +++++ Composition 37 − + + Composition 38 − + + Composition 39 − + +Composition 40 − + +

The control polyurethane (PU) catheter and catheters that did notcontain anti-coagulant showed serious blood aggregation after 1 hour,while the polyurethane catheter containing anti-coagulant showed delayedblood coagulation. As can be seen from the results of Tables 16 and 17,anti-microbial or anti-coagulating effects are maintained even aftermolding processing.

Example 10 Anti-Microbial Polyurethane Prosthetic Feet andAnti-Microbial Test

Anti-microbial polyurethane prosthetic feet were prepared by roll mixingmedical polyurethane resin with anti-microbial materials with thecompositions of Table 18 for 2 hours, introducing it into a mold toreflux for 1 hour while maintaining it at 160° C., and then cooling toroom temperature. Anti-microbial performance was examined by the shakeflask method, and the results are described in Table 19. TABLE 18Compositions of anti-microbial polyurethane prosthetic feet PolyurethaneTotal Anti-microbial resin (wt %) Composition 41 Ciprofioxacin 2.5 97.5100 Composition 42 clinafloxacin 2.5 97.5 100 Composition 43 enoxacin2.5 97.5 100 Composition 44 grepafloxacin 2.5 97.5 100 Composition 45lemefloxacin 2.5 97.5 100 Composition 46 norfloxacin 2.5 97.5 100Composition 47 Pipemidic acid 2.5 97.5 100 Composition 48 sparfloxacin2.5 97.5 100 Composition 49 temafloxacin 2.5 97.5 100 Composition 50tosufloxacin 2.5 97.5 100

TABLE 19 Anti-microbial test for anti-microbial polyurethane prostheticfeet S. aureus E. coli P. aeruginosa (AATC 1621) (AATC 1682) (AATC 2004)Composition 41 99.99 99.99 99.99 Composition 42 99.99 99.99 99.99Composition 43 99.99 99.99 99.99 Composition 44 99.99 99.99 99.99Composition 45 99.99 99.99 99.99 Composition 46 99.99 99.99 99.99Composition 47 99.99 99.99 99.99 Composition 48 99.99 99.99 99.99Composition 49 99.99 99.99 99.99 Composition 50 99.99 99.99 99.99

Example 11 Preparation of Anti-Microbial Gloves and Anti-Microbial Test

Medical gloves were prepared by mixing medical PVC resin withanti-microbials with the compositions of Table 20, and compressing theminto films. Anti-microbial performance was examined by the shake flaskmethod, and the results are as described in Table 21. TABLE 20Compositions of anti-microbial medical gloves Pharmaceutically Totalactive material PVC resin (wt %) Composition 51 Ciprofloxacin 2.5 97.5100 Composition 52 clinafloxacin 2.5 97.5 100 Composition 53 enoxacin2.5 97.5 100 Composition 54 grepafloxacin 2.5 97.5 100 Composition 55lemefloxacin 2.5 97.5 100 Composition 56 norfloxacin 2.5 97.5 100Composition 57 Pipemidic acid 2.5 97.5 100 Composition 58 sparfloxacin2.5 97.5 100 Composition 59 temafloxacin 2.5 97.5 100 Composition 60tosufloxacin 2.5 97.5 100

TABLE 21 Anti-microbial test for anti-microbial gloves S. aureus E. coliP. aeruginosa (AATC 1621) (AATC 1682) (AATC 2004) Composition 51 99.9999.99 99.99 Composition 52 99.99 99.99 99.99 Composition 53 99.99 99.9999.99 Composition 54 99.99 99.99 99.99 Composition 55 99.99 99.99 99.99Composition 56 99.99 99.99 99.99 Composition 57 99.99 99.99 99.99Composition 58 99.99 99.99 99.99 Composition 59 99.99 99.99 99.99Composition 60 99.99 99.99 99.99

Example 12 Preparation of Anti-Microbial Liquid Polymer ResinCompositions

One or two kinds of the anti-microbials ciprofloxacine and norfloxacin,and the anti-fungi/anti-pollutants ketoconazole and fluconazole, werefinely powdered. The anti-microbials were slowly introduced into a mixercontaining a liquid phase resin at room temperature while stirring at ahigh speed to uniformly mix them to prepare a liquid anti-microbialresin composition with the compositions of Table 22 (unit: wt %). TABLE22 Anti-microbial liquid polymer resin compositions Urethane- Acryl-Alkyd- Acryl- Epoxy acrylate melamine melamine polyol Anti-microbialresin¹⁾ resin²⁾ resin³⁾ resin⁴⁾ resin⁵⁾ Ciprofloxacin 1 99 99 99 99 99Norfloxacin 1 99 99 99 99 99 Ketoconazole 0.5 99.5 99.5 99.5 99.5 99.5Norfloxacin 1 + 98.5 98.5 98.5 98.5 98.5 fluconazole 0.5 Ciprofloxacin1 + 98.5 98.5 98.5 98.5 98.5 ketoconazole 0.5Note)¹⁾Samwha paint industry Co. Ltd., product SB-EE-400²⁾Samwha paint industry Co. Ltd., product SB-V-100³⁾Samwha paint industry Co. Ltd., product SB-MA-61⁴⁾Samwha paint industry Co. Ltd., product SB-MA-20⁵⁾Aekyung Chemical Co. Ltd., product BURNOK

Anti-Microbial, Anti-Pollution and Yellowing Tests for Anti-MicrobialLiquid Polymer Resin

The anti-microbial liquid resins prepared in Examples 12 wererespectively coated on a polyethylene sheet and an aluminum plate, andthen each of them was naturally cured, thermally cured, or UV-cured.Anti-microbial, anti-pollution, and yellowing tests were conducted, andthe results are as described in Table 23. TABLE 23 Curing conditions andanti-microbial, yellowing, and anti-pollution test results CompositionComposition 2²⁾ Composition 3³⁾ Composition 4⁴⁾ Curing method naturalthermal UV natural Drying condition 2 hrs 30 min. 8 m/min 2 hrs (20° C.)(150° C. 160° C.) (high pressure (20° C.) mercury lamp 80 W/cm 1 Lamp)Thickness of 40 40 20 40 dried film (μm) Anti-fungi 4 grade 4 grade 4grade 0 grade property⁵⁾ Anti-microbial 7 8.0 7.5 7 property⁶⁾ (mm)Yellowing⁷⁾ pass pass pass pass Anti-polluting — — pass pass property⁸⁾Note)¹⁾ciprofloxacin 1 wt % + epoxy resin 99 wt %²⁾ciprofloxacin 1 wt % + (acryl + melamine resin) 99 wt %³⁾norfloxacin 1 wt % + fluconazole 0.5 wt % + (urethane + acrylateresin) 98.5 wt %⁴⁾ciprofloxacin 1 wt % + ketoconazole 0.5 wt % + epoxy resin 98.5 wt %⁵⁾strain: P. citrinum KCTC 6990 (measured by ASTM G21)Grade: 0 grade - No mold growth on a sample1 grade - Mold grew within 10% on a sample2 grade - Mold grew 10 to 30% on a sample3 grade - Mold grew 30 to 60% on a sample.4 grade - Mold grew 60% or more on a sample.⁶⁾strain and test method: E. coli, KCTC 1682 (ASTM G22 method)⁷⁾yellowing test: measured by ASTM D1925⁸⁾Anti-pollution test: measured by ASTM D5589

Experiment 1 Measurement of Environmental Hormone of MedicalAnti-Microbial Polymer Resin

For the material of the medical appliances of the Examples, whether ornot environmental hormone exists was examined by the EPA 8270 methodusing a GC/MS analyzing apparatus (Shimadzu QP5050A). The results are asdescribed in Table 24. TABLE 24 Test results for detection ofenvironmental hormone Master batch Catheter, Prosthetic feetEnvironmental Composition Composition Composition CompositionComposition Composition Composition hormone 1 2 3 19 20 23 41Diethylphthalate x x x x x x x Di-n-propyl x x x x x x x Phthalate x x xx x x x Di-n-butyl x x x x x x x phthalate Di-n-pentyl x x x x x x xphthalate Di-2-ethylhexyl x x x x x x x phthalate N-buyl benzyl x x x xx x x phthalate Di-2-ethylhexyl x x x x x x x adipate 4-pentyl phenol xx x x x x x 4-octyl phenol x x x x x x x Nonyl phenol x x x x x x xNote)x: No detected environmental hormone●: environmental hormone detected

As can be seen from the results of Table 24, no environmental hormonewas detected from the master batches, catheters, or prosthetic feet,indicating that they are safe for medical appliances.

Experiment 2 Test for Elution of Anti-Microbial Material

For the material of the medical appliances/instruments of Examples, ananti-microbial material elution test was conducted using distilled water(DW) by KFDA 1999-18. The results are as described in Table 25. TABLE 25Anti-microbial material elution test Master batch Catheter, Prostheticfeet Composition 1 Composition 2 Composition 19 Composition 20Composition 41 Measurement of absorbance PASS PASS PASS PASS PASS(250-350 nm): 0.1% or less Non-volatile component: PASS PASS PASS PASSPASS 1 mg 

(0.30 mg) (0.28 mg) (0.31 mg) (0.27 mg) (0.33 mg) Heavy metal contents:ND ND ND ND ND ND pH: 1.0 or less 0.33 0.29 0.35 0.32 0.41

Experiment 3 Measurement of Released Amount of Anti-Microbial orAnti-Coagulating Material

For LLDPE M/B respectively containing 5% and 10% of ciprofloxacin and10% of warfarin, the released amounts of anti-microbial material weremeasured with passage of time. The results are as described in Table 26.TABLE 26 Measurement of released amount of anti-microbial oranti-coagulating material Elution test 3 hrs 48 hrs 120 hrs 240 hrsliquid LLDPE M/B 1.2 ppm 1.5 ppm 1.5 ppm 1.5 ppm H₂O (containing 5%continuous ciprofloxacin) release LLDPE M/B 2.5 ppm 4 ppm 5 ppm   4ppm-5 ppm H₂O (containing 10% continuous ciprofloxacin) release LLDPEM/B 0.9 ppm 1.1 ppm 1.2 ppm 1.6 ppm-1.9 ppm H₂O (containing 10%continuous warfarin) release

As can be seen from Table 26, LLDPE polymer resin continuously releaseda maximum of 5 ppm of anti-microbial material, indicating that a rapidanti-microbial effect decrease can be prevented, thereby increasinganti-microbial effect durability. And, anti-coagulating material showedsimilar results. Such results can solve the toxic problem in a body dueto excessive drug release.

As explained, the present invention mixes commonly used polymers such assilicon, urethane resin, etc. with pharmaceutically active materialsthat are safe to a human body by a simple addition method of non-solventtype instead of the preexisting method of coating an active material onthe surface of a polymer after processing it using an organic solvent.Accordingly, mixing of a commonly used polymer resin and apharmaceutically active material is superior without using a solvent, asuperior anti-microbial effect can be maintained even after hightemperature processing, and a toxic problem due to elution can besolved. Therefore, anti-microbial or anti-coagulating properties can beimparted to industrial appliances, household appliances, petrochemicalssuch as an anti-polluting paint, and natural rubber, as well as tomedical materials.

1. A method for preparing an anti-microbial or anti-coagulating polymerresin comprising the step of mixing a polymer resin with at least onekind of pharmaceutically active material without using a solvent.
 2. Themethod according to claim 1, wherein the pharmaceutically activematerial is contained in an amount of 0.1 to 30 wt % of the totalcomposition.
 3. The method according to claim 1, wherein thepharmaceutically active material is contained in an amount of 0.1 to 20wt % of the composition.
 4. The method according to claim 1, wherein thepharmaceutically active material is an anti-microbial selected from thegroup consisting of grepafloxacin, sparfloxacin, clinafloxacin,enoxacin, lemefloxacin, norfloxacin, pipemidic acid, ciprofloxacin,temafloxacin, tosufloxacin, ketoconazole, itraconazole, econazole,isoconazole, fluconazole, miconazole, terbinafin, a salt thereof, and amixture thereof.
 5. The method according to claim 1, wherein thepharmaceutically active material is an anti-coagulant selected from agroup consisting of warfarin, aspirin, ticlopidine, triflusal,clopidogrel, cilostazole, a salt thereof, and a mixture thereof.
 6. Themethod according to claim 1, wherein the polymer resin is selected froma group consisting of polyetherimide (PEI_, polyethylene (PE),polypropylene (PP), polycarbonate (PC), polyvinylchloride (PVC),polystyrene (PS), epoxy resin, polytetrafluoroethylene (PTFE),polyacetal (POM), polyamide (PA), polyurethane (PU),ethylene-vinylacetate copolymer (EVA), polymethylmethacrylate (PMMA),polyvinylalcohol (PVA), linear low density poly ethylene (LLDPE), lowdensity polyethylene (LDPE), high density polyethylene (HDPE), ABS(acrylonitrile-butadiene-styrene), SAN (styrene-acrylonitrile),polyacrylonitrile, polybutadiene, polyacrylic acid, polyacrylimide,polysulfone, polyacetal, polyamide-imide, polytetrafluoroethylene,polyneoprene, polydimethylsiloxane, polymethylmethacrylate,polyetheretherketone, polyphenylenesulfide, polyvinylfluoride,polyvinylacetate, polyvinylidinefluoride, polyether sulfone,polycaprolactone (PCL) and a copolymer thereof; a silicon resin; anatural rubber; a synthetic rubber; and a mixture thereof.
 7. The methodaccording to claim 1 further comprising the step of adding one or morekinds of additives selected from a group consisting of a dispersant, ananti-oxidant, and a heat stabilizer.
 8. The method according to claim 7,wherein the dispersant is N,N′-ethylene bis stearamide (E.B.S.),polyethylene wax, or a mixture thereof.
 9. A medical polymer resinprepared by the method of claim 1, which has a maximum releaseconcentration of pharmaceutically active material of 10 ppm/100 hrs. 10.A method for preparing an anti-microbial or anti-coagulating medicalappliance comprising the steps of: a) mixing a polymer resin with atleast one kind of pharmaceutically active material without using asolvent; and b) molding and processing the mixture without using asolvent.
 11. The method according to claim 10, wherein thepharmaceutically active material is an anti-microbial selected from agroup consisting of grepafloxacin, sparfloxacin, clinafloxacin,enoxacin, lemefloxacin, pipemidic acid, ciprofloxacin, temafloxacin,tosufloxacin, ketoconazole, itraconazole, econazole, isoconazole,fluconazole, miconazole, terbinafin, a salt thereof, and a mixturethereof.
 12. The method according to claim 10, wherein thepharmaceutically active material is an anti-coagulant selected from agroup consisting of warfarin, aspirin, ticlopidine, triflusal,clopidogrel, cilostazole, a salt thereof, and a mixture thereof.
 13. Themethod according to claim 10, wherein the medical appliance is selectedfrom a group consisting of a silicon catheter, a prosthetic foot, aprosthetic hand, a medical catheter, a surgery glove, artificial skin,an artificial kidney, an artificial articulation, an artificial bone, ablood pack, a tube, a syringe, an artificial tooth, an artificialbone-fixing apparatus, an artificial blood vessel, an artificialfingernail, and an artificial toenail.
 14. The method according to claim10, wherein the method comprises the steps of mixing a silicon resinwith a pharmaceutically active material, and molding and processing themixture at a maximum temperature of 600° C./sec without using a solventto prepare a silicon catheter.
 15. An anti-microbial or anti-coagulatingmedical appliance prepared by the method of claim
 10. 16. The medicalappliance according to claim 15, wherein the medical appliance has amaximum release concentration of pharmaceutically active material of 10ppm/100 hrs.
 17. A method for preparing a master batch or compoundcomprising the steps of: mixing a resin selected from a group consistingof linear low density polyethylene (LLDPE), polypropylene (PP),polyethylene (PE), ABS, polycarbonate (PC), polystyrene (PS), andpolyvinylchloride (PVC) resin with at least one kind of pharmaceuticallyactive material without using a solvent; and molding and processing themixture at 100 to 300° C. to prepare a master batch (M/B) or compound.18. The medical appliance according to claim 17, wherein thepharmaceutically active material is an anti-microbial selected from agroup consisting of grepafloxacin, sparfloxacin, clinafloxacin,enoxacin, lemefloxacin, norfloxacin, pipemidic acid, ciprofloxacin,temafloxacin, tosufloxacin, ketoconazole, itraconazole, econazole,isoconazole, fluconazole, miconazole, terbinafin, a salt thereof, and amixture thereof.
 19. The medical appliance according to claim 17,wherein the pharmaceutically active material is an anti-coagulantselected from a group consisting of warfarin, aspirin, ticlopidine,triflusal, clopidogrel, cilostazole, a salt thereof, and a mixturethereof.
 20. A master batch or compound prepared by the method of claim17.
 21. The master batch or compound according to claim 20, wherein themaster batch or compound is used in any selected from a group consistingof a water-purifying apparatus, a cutting board, a food packaging film,a food container, a refrigerator, a washing machine, a computer andperipheral device, a drinking water tank, a water tub, bidet nozzle anda urinal cover, desk and chair, an automobile handle, infant goods, abath tub, and a cosmetic container.
 22. A method for preparing paintcomprising the step of mixing an anti-microbial selected from a groupconsisting of grepafloxacin, sparfloxacin, clinafloxacin, enoxacin,lemefloxacin, norfloxacin, pipemidic acid, ciprofloxacin, temafloxacin,tosufloxacin, ketoconazole, itraconazole, econazole, isoconazole,fluconazole, miconazole, terbinafin, a salt thereof, and a mixturethereof, with a polymer resin selected from a group consisting of alkydresin, acryl resin, urethane resin, epoxy resin, phenol resin, urearesin, melamine resin, modified resin thereof, and a mixture thereof.23. The method according to claim 22 further comprising the step ofadding one or more kinds of additives selected from a group consistingof a pigment, a diluent, and physical property controlling monomer andoligomer, and polyol.